1. Field of the Invention
This invention lies in the field of methods for the preparation of therapeutic aqueous solutions which contain dissolved therein at the time of use unstable metabolites of the type normally present in human blood plasma, and also to the field of filled storable containers useful for the storage of such solutions in unit dose forms.
2. Prior Art
Previously, I have provided a family of redox active electrolyte fluid compositions which are useful in therapeutic treatment of mammals and man; see my copending U.S. patent applications identified by Ser. Nos. 747,858, 748,232, 748,184 and 747,792, all filed Jun. 24, 1985, and U.S. patent application Ser. No. 810,918, filed Dec. 18, 1985. The teachings of these applications are incorporated herein by reference.
In addition, I have currently provided parenteral nutrition fluids which contain organic nitrogen compounds, such as amino acids, and the like; see, for example, my concurrently filed U.S. patent application identified by Ser. No. 810,918, filed Dec. 18, 1985.
As those skilled in the art will understand, these fluid compositions employ redox active agents which are in the nature of metabolites and which are normally present in human blood plasma. These agents include (1) metabolizable ketoacid anions which are unstable because of a tendency to decarboxylate and lose carbon dioxide in aqueous solution, (2) metabolizable sulfhydryl amino acids which dimerize and/or oxidize, and (3) dissolved carbon dioxide which escapes from aqueous solutions in which it is dissolved at a concentration above ambient by diffusing into the atmosphere upon standing. As such above referenced other copending applications show, examples of such ketoacid anions include pyruvate, acetoacetate, alpha ketoglutarate, and the like. An example of a sulfhydryl containing amino acid is cysteine.
These characteristics make it very difficult to formulate, package and store fluid systems utilizing these redox active agents. In order to provide dose units of such fluid systems which contain such unstable and/or diffusable metabolites in a substantially non-degraded condition after a period of storage, it is necessary to have storable packaged dose units which can be administered to a patient and wherein the dose unit components are maintainable in a condition equal to a freshly prepared state.
Flexible walled containers incorporating plastics and/or metal foil are currently of growing interest in medical environments and the like. Heretofore, various plastic containers containing integrally a plurality of chambers have been provided for storage of therapeutic materials. Each chamber holds one or a group of separatable components which are admixed into a common solution by chamber wall rupture internally before the solution is used. See, for example, PCT publication number WO85/01268 published Mar. 28, 1985 and references cited therein.
Typically, such plastic containers appear to be formed of materials through which carbon dioxide is diffusable; hence, such containers are not suitable for use with the present invention. So far as is known, no one has heretofore ever faced the problems of formulating unstable and/or diffusable redox active metabolites into therapeutic fluids and of providing plastic containers for storing such formulations. Unless these problems can be simply and reliably solved, particularly so as to provide the capability for achieving storable unit dosages, it may not be possible to use my new fluid compositions on a large scale in human medicine.
Surprisingly and unexpectedly, however, it has now been discovered that simple and reliable methods can be employed to fill certain types of plastic bags with my new fluid compositions, thereby to produce filled containers which are capable of long storage of my solutions and of precursors therefor. Thus, my solutions can be administered to patients even after prolonged storage in an optimum and desired state. Thus, for example, such a container having two or more chambers for the separate storage and selective mixing of two precursor components is now usable in such a way as to produce dispensable dosage units of my solutions.